Two separate projects are proposed, one on channel selectivity, and the other on channel gating. The goal of the selectivity project is to measure the permeabilities of a variety of ions for the snail neuron potassium (delayed rectifier) channel, and to interpret these permeabilities with a new selectivity theory. This new theory has certain advantages over prior approaches and should permit us to make inferences about the nature of the molecular groups participating in ion selectivity. The preparation we will use is the voltage clamped and internally perfused snail neuron soma; permeabilities are to be estimated from the bi-ionic potentials. We will test alkali metal and alkaline earth cations for permeability, along with thalium, ammonium and appropriate small organic cations (hydrazine, hydroxylamine, methylamine guanidine). We will attempt to extend the quantitative treatment to include the permeabilities of these later ions. The goal of the gating project is to develop a molecular theory that will account for nerve excitability. We will study sodium channel ionic currents, gating currents, and current fluctuations in a frog node treated with sea anemonae toxin to slow sodium inactivation. The quantitative theory treats membrane channel proteins that are envisioned as taking on several conformational states, one of which is associated with the open channel; the membrane electric field drives the protein to its open conformation through interactions of the field with protein dipole moments associated with the various conformational states. The theory will be tested by estimating constants from ionic current data, and then using these constants to predict gating currents and the covariance function for the current fluctuations.